PMID- 32905620
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211220
IS  - 1472-8206 (Electronic)
IS  - 0767-3981 (Linking)
VI  - 35
IP  - 4
DP  - 2021 Aug
TI  - Metformin potentiates the chemotherapeutic effects of doxorubicin on 
      2-amino-1-methyl-6-phenylimidazo[4,5b] pyridine-induced Mammary Carcinoma in 
      rats.
PG  - 700-713
LID - 10.1111/fcp.12604 [doi]
AB  - This study was carried out to evaluate the antitumor activity of Metformin (Met) 
      and its impending utility to potentiate the chemotherapeutic action of 
      doxorubicin on 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP)-induced rat 
      mammary carcinogenesis. Female Sprague -Dawley (SD) rats were divided into seven 
      groups (n = 15 each). Mammary carcinogenesis was induced by the administration of 
      PhIP at a dose of 75 mg/kg by gavage. Met treatment was 2 mg/ml in drinking water 
      for 26 weeks started after the last PhIP dose. Doxorubicin (Dox) treatment 
      started after one month of the last PhIP dose with a dose of 4 mg/kg, i.v. once 
      per week for 4 weeks. Compared to the PhIP group, the latency period of tumors in 
      the PhIP+Dox, PhIP+Met, and PhIP+Dox+Met groups were significantly increased and 
      tumors' incidences and multiplicities were significantly reduced. By 
      immunohistochemistry, carcinomas from the combination treatment groups showed a 
      significant decrease in the labeling indexes (LI%) of cellular proliferation and 
      CD44 compared to the PhIP group while LI% for ERalpha was significantly decreased in 
      all combination treatment groups compared to the PhIP-administered group. 
      Moreover, the quantitative mRNA expression of ERalpha was significantly decreased in 
      mammary tumors from PhIP + Dox+Met combined group more than the PhIP + Dox group. 
      However, mRNA expression of EGF was found significantly lower in all combination 
      treatment groups compared to the PhIP group. These findings suggest that 
      Metformin potentiate the antitumor efficacy of doxorubicin and had beneficial 
      effects on PhIP-induced mammary carcinogenesis through the prevention of cellular 
      proliferation and mRNA expression of ERalpha and EGF.
CI  - (c) 2020 Societe Francaise de Pharmacologie et de Therapeutique.
FAU - Salim, Elsayed
AU  - Salim E
AD  - Department of Zoology, Faculty of Science, Tanta University, Tanta, 31527, Egypt.
FAU - El-Sisi, Alaa El-Din
AU  - El-Sisi AE
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, 
      Tanta, 31527, Egypt.
FAU - Sokar, Samia
AU  - Sokar S
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, 
      Tanta, 31527, Egypt.
FAU - El-Sayad, Magda
AU  - El-Sayad M
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, 
      Tanta, 31527, Egypt.
FAU - Moussa, Ethar
AU  - Moussa E
AUID- ORCID: 0000-0001-8734-9886
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, 
      Tanta, 31527, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20201205
PL  - England
TA  - Fundam Clin Pharmacol
JT  - Fundamental & clinical pharmacology
JID - 8710411
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Imidazoles)
RN  - 80168379AG (Doxorubicin)
RN  - 909C6UN66T (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/administration & dosage/*therapeutic use
MH  - Doxorubicin/administration & dosage/*therapeutic use
MH  - Drug Synergism
MH  - Female
MH  - Hypoglycemic Agents/administration & dosage/*therapeutic use
MH  - Imidazoles
MH  - Mammary Neoplasms, Experimental/chemically induced/*drug therapy
MH  - Metformin/administration & dosage/*therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - CD44
OT  - Doxorubicin
OT  - ERalpha
OT  - Mammary carcinoma
OT  - Metformin
OT  - PCNA
EDAT- 2020/09/10 06:00
MHDA- 2021/12/21 06:00
CRDT- 2020/09/09 18:16
PHST- 2020/08/20 00:00 [revised]
PHST- 2020/06/08 00:00 [received]
PHST- 2020/09/02 00:00 [accepted]
PHST- 2020/09/10 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2020/09/09 18:16 [entrez]
AID - 10.1111/fcp.12604 [doi]
PST - ppublish
SO  - Fundam Clin Pharmacol. 2021 Aug;35(4):700-713. doi: 10.1111/fcp.12604. Epub 2020 
      Dec 5.